1. Field of the Invention
The invention generally relates to compounds, compositions and methods for the treatment of cancerous cells. More specifically, the invention relates compounds, compositions and methods for iron-based cancer photodynamic therapy.
2. Description of the Relevant Art
Exogenous agents that rapidly elevate reactive oxygen species (ROS) above toxic threshold levels has been touted as a potentially effective, but largely untested cancer therapeutic strategy.
“Free” ferrous iron is known to produce cell-damaging ROS, principally hydroxyl radical, via the Fenton reaction in which hydrogen peroxide produced as a byproduct of oxygen metabolism is one-electron reduced by Fe2+. The Fenton-derived hydroxyl radicals damage lipids, proteins and DNA even at sub-micromolar steady-state levels of hydrogen peroxide and free iron. The Fe3+ product of the Fenton reaction is rapidly re-reduced to Fe2+ by intracellular reductants, so that this Fenton generation of hydroxyl radical is catalytic.
One rationale for the limited effectiveness of singlet oxygen photodynamic therapy is that it requires well-oxygenated tissues, whereas many tumor environments tend to be hypoxic. Intracellular Fenton chemistry, on the other hand, occurs at toxic levels even under hypoxic conditions at relatively low (micromolar or lower) levels of hydrogen peroxide and “free” iron. Furthermore, hypoxia results in a relatively reducing environment, which would facilitate the catalytic Fenton chemistry mentioned above. Iron and hydrogen peroxide are relatively small “drugs” and could conceivably penetrate the interior of solid tumors more efficiently than traditional “small molecule” organic drugs.
Published tumor targeting methods typically use antibodies to tumor cell surface proteins or so-called tumor-targeting peptides (TTPs), which bind to specific cell surface receptors that are often hyperexpressed in tumors. Numerous TTPs have been reported. Particles containing multiple tumor targeting moieties have been shown to be more effective as tumor selective agents than the corresponding monomers.